Hypothyroidism: causes
- Mechanism
Too little thyroid hormone slows the body. In babies it harms brain growth, so newborns are screened.
What it is
Hypothyroidism results from structural or functional loss of thyroid hormone production, usually in the gland itself (primary) and rarely from pituitary or hypothalamic failure (central). Worldwide, iodine deficiency remains the leading cause; where iodine is sufficient, Hashimoto thyroiditis dominates. In infancy it causes cretinism, with irreversible intellectual disability if untreated; in adults, myxoedema.
Step by step
- Iodine is trapped, oxidised and attached to thyroglobulin by thyroid peroxidase; defects at any step reduce hormone.
- Falling T4 and T3 remove feedback, so TSH rises in primary disease.
- High TSH stimulates follicular growth, which can produce a goitre when synthesis is blocked.
- Low hormone slows metabolism and reduces glycosaminoglycan clearance in the dermis and organs.
- Glycosaminoglycans and water accumulate: myxoedema, hoarse voice, pericardial effusion.
Why the thyroid fails
| Level | Examples | TSH |
|---|---|---|
| Thyroid tissue destroyed | Hashimoto, surgery, radioiodine, radiation | High |
| Thyroid never formed or misplaced | Agenesis, hypoplasia, lingual thyroid | High |
| Hormone cannot be made | Iodine deficiency, TPO or thyroglobulin defects, drugs | High (with goitre) |
| Pituitary or hypothalamus | Pituitary tumours, Sheehan syndrome, surgery | Low or normal |
| Severe systemic illness (adaptive) | Euthyroid sick syndrome | Normal or low; low T3 |
Clinical notes
- Newborn screening (heel-prick TSH) is the reason cretinism is now rare where it exists.
- Myxoedema coma: hypothermia, hypoventilation, hyponatraemia and coma, often triggered by infection or cold.
- Latin America: iodised salt programmes have greatly reduced endemic goitre and cretinism, but pockets remain.
Test yourself
Think of the answer, then tap the question to see it.
Which pattern of TSH and free T4 shows central hypothyroidism?
Low free T4 with a low or inappropriately normal TSH.
What substance accumulates in myxoedema?
Glycosaminoglycans (hyaluronic acid) with water in the dermis and other tissues.
What are two causes of congenital hypothyroidism?
Thyroid dysgenesis (agenesis, hypoplasia, ectopic thyroid) and dyshormonogenesis such as TPO defects; also severe maternal iodine deficiency.
Elsewhere in DurgiPedia
- Thyroid hormone synthesis
- Thyroid peroxidase (TPO)
- Thyroid gland: from the foramen cecum to the neck
- The thyroid axis: reading TSH and free T4
- Thyroglossal duct cyst and ectopic thyroid
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Hypothyroidism (StatPearls (NCBI Bookshelf), 2025); Thyroid Diseases (MedlinePlus, US National Library of Medicine, 2025).
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Representative model, for educational purposes only.